Leishmaniasis is a protozoan vector borne parasitic disease caused by protozoan parasites of the genus Leishmania and is transmitted through the bite of certain species of Phlembotominae sandfly. Of the approximately 30 species of Leishmania known to infect mammals, 21 of these species are believed to cause leishmaniasis in humans. Leishmaniasis has been reported on all continents except Australia and Antarctica, and has been found in parts of about 88 countries. Leishmaniasis is primarily a disease of the developing countries, and is more rare in the developed world. However, cases have been reported in military personnel who have served in the Persian Gulf. In the Americas, leishmaniasis can be found in Mexico and South America, but has recently been shown to be spreading to Texas.
Leishmaniasis manifests in three distinct forms including; cutaneous leishmaniasis (CL), visceral leishmaniasis (VL) and mucocutaneous leishmaniasis (ML). Of the three variants recognized by the Centers for Disease Control and Prevention (CDC), CL and VL are considered endemic diseases in tropical and subtropical regions throughout the world. Leishmaniasis threatens approximately 350 million humans in nearly 90 countries. Currently, approximately 12 million humans are believed to be infected, with over 2 million new cases being reported each year. Leishmaniasis disproportionally affects the poorest inhabitants of the world and significantly hinders the economic development of these developing societies.
Due to the complex life cycles of the causative parasites, leishmaniasis is rarely diagnosed in its early stages when therapeutic intervention is most effective. Leishmaniasis typically presents as skin sores or ulcers which erupt weeks to months after the person is bitten. However, if left untreated, the infection can progress and lead to splenomegaly, liver damage, renal damage, anemia, and death.
Therapeutic compounds containing antimony, specifically pentavalent antimonials (e.g., meglumine antimonate and sodium stibogluconate) were the first drugs introduced to treat leishmaniasis, and they remain the first-line therapeutic approach in many parts of the world. However, use of pentavalent antimonials is associated with significant adverse effects and are administered by intravenous or intramuscular injection. Moreover, the use of these drugs as first-line therapy for over 50 years has resulted in the emergence of drug-resistant parasites.
Unfortunately, despite the significant prevalence of this disease throughout large portions of the world, there remains a scarcity of therapeutic agents that have potent activity against Leishmania species with minimal adverse effect on the patient and an efficient route of administration. Therefore, there remains a need for methods and compositions that overcome these deficiencies and that provide a therapeutic alternative for leishmaniasis.